Pharmaceuticals intended for oral administration are typically provided in solid form as tablets, capsules, pills, lozenges, or granules. Tablets are swallowed whole, chewed in the mouth, or dissolved in the oral cavity. Chewable tablets are typically made from a mixture including active drug particles, and other inactive ingredients (excipients), and are often employed for the administration of pharmaceuticals where it is impractical to provide a tablet for swallowing whole. With chewable tablets, the act of chewing helps to break up the tablet particles as the tablet disintegrates and may increase the rate of absorption by the digestive tract. Chewable tablets are often utilized to improve drug administration in pediatric and geriatric patients.
Certain drug particles have a bitter or otherwise unpleasant taste. In order to make chewable tablets from these, their taste must be masked for example by dispersing or coating the particles with a coating composition. Depending on the nature of the coating composition, the dissolution or release profile of the particles and tablets made therefrom can be changed.
For example, U.S. Pat. No. 5,536,507 to Abramowitz et al. relates to a three component pharmaceutical formulation containing one or more pharmacologically active substances such that greater than 80% of the active substance will be released in the large intestine. The formulation comprises a core comprising the pharmacologically active substance, microcrystalline cellulose, a pH-sensitive polymer, and optionally an osmotic agent. Over the core is a delayed release coating comprising a non-water soluble polymer such as Eudragit RS30D (poly(ethyl acrylate, methyl methacrylate)trimethylammonioethyl methacrylate chloride)) or ethylcellulose, a plasticizer and an antiagglomerating agent. Over the delayed release coating is an enteric coating such as cellulose acetate phthalate, cellulose acetate trimetallate, or Eudragit L30D (poly(methacrylic acid, ethyl acrylate)).
U.S. Pat. No. 5,681,584 to Savastano et al. relates to another delayed release drug delivery device. In this case, the targeted site for drug delivery is within the gastrointestinal tract, particularly the colon. The device consists of a solid core comprising an active ingredient coated with three separate layers: 1) a delay jacket comprising a binder, an osmotic agent and a lubricant; 2) a semipermeable membrane that may be made of cellulose acetate, ethyl cellulose, cellulose acetate phthalate, or Eudragit NE30D (poly(ethyl acrylate, methyl methacrylate)), Eudragit RL (poly(ethyl acrylate, methyl methacrylate)trimethylammonioethyl methacrylate chloride) or Eudragit RS (poly(ethyl acrylate, methyl methacrylate)trimethylammonioethyl methacrylate chloride); and 3) an enteric polymer such as cellulose acetate phthalate or hydroxypropyl methylcellulose phthalate.
Canadian Appln. No. 2,068,366 describes a microcapsule composition and process for making the same. The dissolution profile of the microcapsule is reduced by approximately 25%, preferably approximately 40%, more preferably approximately 50%, relative to a standard microencapsulated tablet when measured at a pH of about 6.8. The microcapsule composition of Canadian Appln. No. 2,068,366 is made by spray drying a suspension or dispersion of a pharmaceutically active ingredient in a coating solution. The coating solution contains 3 to 75 wt % of a water insoluble polymer. The coating solution may optionally contain an enteric, reverse enteric, or water soluble polymer as well. In Example 3 of the application, an enteric coating comprising ethylcellulose, hydroxypropyl methylcellulose acetate succinate and dicloromethane was spray dried with sodium diclofenac. The release profile of the enteric coated diclofenac, shown in FIG. 3, indicates that less than 80% of the drug had been released after 30 minutes in a pH 7.5 solution.
U.S. Pat. No. 4,800,087 to Mehta relates to taste-masked pharmaceutical compositions in which pharmaceutically active compound is microencapsulated with a polymer coating. The polymer coating comprises a high temperature film forming polymer in combination with either a plasticizer or a low temperature film forming polymer. The high temperature film forming polymer may be ethyl cellulose or another cellulose polymer or preferably Eudragit L30D, which is an enteric polymer. The low temperature film forming polymer is preferably Eudragit NE30D, which is a nonenteric polymer that swells in aqueous solution.
Applicants have now discovered that taste masked pharmaceutical formulations having an immediate release profile may be made using a continuous polymeric coating comprising a mixture of an enteric polymer and an insoluble film forming polymer. The polymeric coating is used to cover the entire surface of drug particles, such that the surfaces of the particles are substantially free of active ingredient. The coated particles of the invention advantageously exhibit sufficient elasticity without the need for plasticizer to maintain integrity during tableting and prevent release of the drug into the mouth during chewing. Chewable tablets made from these coated particles have excellent taste and yet surprisingly exhibit an immediate release profile.